The action of morphine at the subcellular and molecular level is being studied in order to understand mechanisms of tolerance and dependence to narcotic analgesic drugs. The nerve terminal membrane has been proposed as the primary site of action of many pharmacological agents. Thus, synaptosomes (which arise from the pinching off and resealing of nerve endings) as well as subsynaptosomal components are being used to characterize biochemical, functional, and morphologic changes associated with the tolerant-dependent state. In particular, the effects of acute and chronic morphine treatment on the turnover rates of various brain protein subfractions are being determined.